US12145957B2ActiveUtilityA1
Preparation method for glufosinate
Est. expiryJul 20, 2041(~15 yrs left)· nominal 20-yr term from priority
C07C 323/59C07C 323/32C07C 237/06C07C 271/22C07F 9/5407C07B 2200/07C07F 9/301C07F 9/30C07F 9/32
64
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0
Cited by
16
References
30
Claims
Abstract
A preparation method for glufosinate or a salt, an enantiomer or a mixture of enantiomers in all ratios thereof, the method being especially suitable for the preparation of glufosinate, and greatly shortening steps in an existing preparation process. Especially in the preparation of L-glufosinate, the product can effectively retain the ee value of the raw materials.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A method for preparing a glufosinate compound of formula (I), a salt thereof, an enantiomer thereof, or a mixture of enantiomers thereof, which enantiomers may be present in any ratio,
wherein the method comprises the following steps:
a) reacting a compound of formula (II) or a salt thereof, an enantiomer thereof or a mixture of enantiomers thereof, which enantiomers may be present in any ratio,
with one or more compounds of formula (III) or a mixture; wherein said mixture comprises one or more compounds of formula (IV) and one or more compounds of formula (V); or one or more compounds of formula (IV) and one or more compounds of formula (III); or one or more compounds of formula (V) and one or more compounds of formula (III); or one or more compounds of formula (III), one or more compounds of formula (IV), and one or more compounds of formula (V),
wherein the reaction of a) results in a “reaction intermediate”;
b) reacting the reaction intermediate which results from step a), wherein said reaction intermediate may or may not be in isolated form, with an acid or a base to obtain a glufosinate compound of formula (I) or a salt thereof, an enantiomer thereof, or a mixture of enantiomers thereof, which enantiomers may be present in any ratio;
wherein when PG is an amino protecting group, the method further optionally includes the removal of the amino protecting group;
further wherein:
LG is Hal 1 , —OTs or Hal 1
Hal 1 and Hal 2 are each independently halogen selected from fluorine, chlorine, bromine or iodine;
PG is hydrogen or an amino protecting group selected from —C(═O)R, —C(═O)OR and —S(═O) 2 R;
A is —NHR 1 , —NR 1 R 1′ , or —OR 1 ;
R, R 1 , R 1′ , R 2 , R 3 and R 4 are each independently selected from the group consisting of C 1 -C 6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, C 6-12 aralkyl, 5- to 14-membered heteroaryl and 3- to 10-membered heterocyclyl,
with the further proviso that when the mixture comprises a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture of one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); then
R 2 is either R 3 or R 4 ; and
the chiral carbon atom is labeled with *; and
with the further proviso that at least one of the following conditions is met:
1) the compound of formula (II) is not
2) the compound of formula (III) is not
3) the compound of formula (IV) is not
4) the compound of formula (V) is not
2. The method according to claim 1 , wherein the glufosinate compound of formula (I) or salt thereof which results from the method is enantiomerically pure,
and wherein the compound of formula (II) in step a) is enantiomerically pure.
3. The method according to claim 1 , wherein the enantiomeric ratio of (L):(D)-enantiomer or (D):(L)-enantiomer ranges from 50.5:49.5 to 99.5:0.5.
4. The method according to claim 1 , wherein R is C 1-6 alkyl or C 6-10 aryl.
5. The method according to claim 1 , wherein LG is chlorine, bromine, iodine, —OTs or
6. The method according to claim 1 , wherein R 1 , R 1′ , R 2 , R 3 and R 4 are each independently C 1 -C 6 alkyl or C 6-12 aralkyl.
7. The method according to claim 1 , wherein
R 1 and R 1′ are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or benzyl; or
A is —NHCH 2 CH 2 CH 2 CH 3 , —N(CH 3 ) 2 , —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH(CH 3 ) 2 , —OCH 2 CH 2 CH 2 CH 3 , —OCH 2 CH(CH 3 ) 2 or —OBn.
8. The method according to claim 1 , wherein
R 2 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; or
R 3 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; or
R 4 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.
9. The method according to claim 1 , wherein the mixture comprises one or more compounds of formula (IV) and one or more compounds of formula (III), and the molar ratio of the compounds of formula (IV) to the compounds of formula (III) ranges from 0.9:1 to 1.1:1 or 0.05:1 to 1.1:1; or the mixture comprises one or more compounds of formula (V) and one or more compounds of formula (III), and the molar ratio of the compounds of formula (V) to the compounds of formula (III) ranges from 0.9:1 to 1.1:1 or 0.05:1 to 1.1:1; or the mixture comprises one or more compounds of formula (IV) and one or more compounds of formula (V), and the molar ratio of the compounds of formula (IV) to the compounds of formula (V) ranges from 0.9:1 to 1.1:1.
10. The method according to claim 1 , where in step a), the reaction temperature ranges from 20° C. to 200° C.
11. The method according to claim 1 , where the reaction of step a) is conducted in the presence of a base.
12. The method according to claim 11 , wherein the base in the reaction of step a) is an organic base selected from the group consisting of an organic amine, pyridine or a pyridine derivative having 1-3 substituents attached to one or more carbon atoms in the heterocycle, piperidine or a piperidine derivative having 1-3 substituents attached to one or more carbon atoms in the heterocycle or ammonia.
13. The method according to claim 12 , wherein the organic base is selected from the group consisting of triethylamine, piperidine and pyridine.
14. The method according to claim 1 , wherein in step a), the molar ratio of the base to the total amount of the compound of formula (III) and the compound of formula (V) ranges from 1:1 to 10:1.
15. The method according to claim 1 , wherein in step a), the reaction is conducted under solvent-free conditions or in the presence of an inert solvent.
16. The method according to claim 15 , wherein in step a), the inert solvent is selected from any one or more of benzene solvents, amide solvents, hydrocarbon solvents, halogenated hydrocarbon solvents, sulfone or sulfoxide solvents, ether solvents or ester solvents.
17. The method according to claim 15 , wherein in step a), the inert solvent comprises one or more of chlorobenzene, trimethylbenzene, 1,4-dioxane, 1,2-dichloroethane, dimethyl sulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, petroleum ether, n-heptane, tetrahydrofuran, methyltetrahydrofuran, benzene, toluene, ethyl acetate, and butyl acetate.
18. The method according to claim 1 , wherein in step a), the molar ratio of the compound of formula (III) or the mixture to the compound of formula (II) ranges from 1:0.8 to 1:10; or the molar ratio of the compound of formula (II) to the compound of formula (III) or the mixture ranges from 1:0.8 to 1:10.
19. The method according to claim 1 , wherein in step b), an inorganic acid or organic acid is added.
20. The method according to claim 19 , wherein the inorganic acid is hydrochloric acid or sulfuric acid.
21. The method according to claim 1 , wherein in step b), the base is an inorganic or organic base, wherein the inorganic base is selected from the group consisting of alkali metal hydroxide, alkali-earth metal hydroxide, alkali metal carbonate, alkali-earth metal carbonate, alkali metal bicarbonate and alkali-earth metal bicarbonate.
22. The method according to claim 21 , wherein the base is NaOH, KOH or Ba(OH) 2 .
23. The method according to claim 1 , wherein in step b), the reaction temperature ranges from 20 to 150° C.
24. The method according to claim 1 , wherein the compound of formula (II) is selected from the group consisting of:
No.
The compound of formula (II)
1.
2.
3.
4.
5.
6
7.
8.
9.
10.
11.
12.
13.
14.
and/or,
the compound of formula IV is
and/or the compound of formula (V) is
25. A compound of formula (II) or a salt thereof,
wherein the compound of formula (II) is selected from the group consisting of:
26. The method according to claim 4 , wherein R is methyl, ethyl, tert-butyl, phenyl or p-methylphenyl.
27. The method according to claim 1 , wherein the PG is hydrogen, —C(═O)CH 3 , —C(═O)Ph, —C(═O)OC 2 H 5 , —C(═O)OC(CH 3 ) 3 or
28. The method according to claim 6 , wherein R 1 , R 1′ , R 2 , R 3 and R 4 are each independently C 1 -C 4 alkyl or benzyl.
29. The method according to claim 1 , wherein in step a), the reaction temperature ranges from 90° C. to 140° C.
30. The method according to claim 1 , wherein in step a), the molar ratio of the compound of formula (III) or the mixture to the compound of formula (II) ranges from 1:1 to 1:3; or the molar ratio of the compound of formula (II) to the compound of formula (III) or the mixture ranges from 1:1 to 1:3.Cited by (0)
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